克里唑替尼及其中间产物的优化合成研究

Study on Optimal Synthesis of Crizotinib and Its Intermediate Products

优化了克里唑替尼的合成路线,以3-羟基-5-溴-2-硝基吡啶为起始原料,经Mitsunobu反应后,通过酯化引入吡啶环结构,再经过氨基保护作用,发生Suzuki偶联反应得到终产物。以中间产物3为对象,讨论反应温度、反应时间、pH对得率的影响;从单因素考虑,分别在反应温度90℃、反应时间13 h、结晶pH 5.5时得率最高,经测定中间产物得率为89.3%。

The synthetic route of crizotinib was optimized.With 3-hydroxy-5-bromo-2-nitropyridine as the starting material,the pyridine ring structure was introduced through esterification after Mitsunobu reaction,and then Suzuki coupling reaction occurred after amino protection.The effects of reaction temperature,reaction time and pH on the yield of intermediate 3 were discussed.Considered the single factor,the yield was the highest when the reaction temperature was 90℃,the reaction time was 13 h and the crystallization pH was 5.5.The yield of intermediate was 89.3%.